The genetic control and immunologic mechanisms of autoimmune disease is being investigated in the New Zealand stains of mice, their F1 hybrids, and recombinant-inbred lines derived from them. We have found 1) that enlargement of Lyt-2+ T cells is significantly asociated with the titer of anti-erythrocyte autoantibody and degree of hemolytic anemia; 2) T cell suppression is defective in old NZB mice; 3) NZB, and particularly the (NZB x NZW) F1 hybrid, mice have a major resistance to induction of tolerance in the T cell subpopulation; 4) Several abnormalities of proteins synthesized by lymphocytes from NZB mice can be demostrated by two-dimensional gel electrophoresis. One, a 16 kd fragment of kappa chain, is observed only in enlarged NZB B cells.